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Antipsychotic Drugs

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  • 1

  • Schizophrenia

    affecting about 7 per thousand of the adult population

    mostly in the age group 15-35 years

    the incidence is low (3-10,000), the prevalence is high due to chronicity

    about 24 million people wordwide

    More than 50% of persons with schizophrenia are not receiving appropriate care

    90% of people with untreated schizophrenia are in developing countries

    2

  • Prescription for an antipsychotic

    Physician Specialty Estimated %

    Psychiatry 70.31%

    General family practice 11.46%

    Internal medicine 9.99%

    Pediatrics 0.68%

    Neurology 1.50%

    Other specialties 6.10%

    Outpatient Use of Major Antipsychotic Drugs in Ambulatory Care Settings in the United

    States, 1997-2000

    3

  • /

    ,

    05

    enicideM ycnegremE s'illanitniT 4

  • Indications

    5

  • Antipsychotic drugs

    First generation

    Low-potency

    Chlorpromazine (Taroctyl )

    Thioridazine (Ridazin )

    Midpotency Trifluoperazine

    Perphenazine (Perphenan )

    Loxapine

    Molindone

    Highpotency Haloperidol (Haldol )

    Fluphenazine (Fludecate )

    Thiothixene

    Second generation

    Clozapine (Leponex, Lozapine )

    Risperidone (Risperdal )

    Olanzapine (Zyprexa )

    Quetiapine (Seroquel )

    Ziprasidone (Geodon )

    Aripiprazole (Abilify )

    Paliperidone (Xeplion )

    Iloperidone

    Asenapine

    Lurasidone

    6

  • 7Antipsychotic Medications

    aripiprazole 10 and older for bipolar disorder, manic or mixed episodes;13 to 17 for schizophrenia and bipolar;

    chlorpromazine 18 and older

    clozapine 18 and older

    fluphenazine (generic only) 18 and older

    haloperidol 3 and older

    iloperidone 18 and older

    loxapine 18 and older

    molindone 18 and older

    olanzapine 18 and older; ages 13-17 as second line treatmentfor manic or mixed episodes of bipolar disorder and

    schizophrenia

    paliperidone 18 and older

    perphenazine (generic only) 18 and older

    pimozide (for Tourette's syndrome) 12 and older

    quetiapine 13 and older for schizophrenia;18 and older for bipolar disorder;

    10-17 for treatment of manic and mixed episodes of bipolar disorder

    risperidone 13 and older for schizophrenia;10 and older for bipolar mania and mixed episodes;

    5 to 16 for irritability associated with autism

    thioridazine (generic only) 2 and older

    thiothixene 18 and older

    trifluoperazine 18 and older

    ziprasidone 18 and older NIMH

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    21

  • First generation

    Extrapyramidal side effects Metabolic disorders

    Second generation

    Metabolic disorders Extrapyramidal side effects

    13Clinical pharmacology & Therapeutics | VOLUME 90 NUMBER 1 | July 2011

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    41

  • Motor side effects of typical antipsychotics

    15

  • 16

  • 17

    ORAL DOSAGE (mg/day)

    ACUTE PSYCHOSIS MAINTENANCE METABOLIC SIDE EFFECTS

    Dosage Forms 1ST Episode Chronic 1ST Episode Chronic Weight Gain Lipids Glucose

    Typical Antipsychotic Agents

    ChlorpromazineO, S, IM

    200-600 400800 150-600 250-750 +++ +++ ++

    PerphenazineO, S, IM

    12-50 24-48 12-48 24-60 /+

    TrifluoperazineO, S, IM

    5-30 10-40 2.5-20 10-30 /+

    FluphenazineO, S, IM

    2.5-15 5-20 2.5-10 5-15 /+

    FluphenazinedecanoateDepot IM

    Not for acute use 5-75 mg/2 wks /+

    MolindoneO, S

    15-50 30-60 15-50 30-60

    LoxapineO, S, IM

    15-50 30-60 15-50 30-60 +

    Haloperidol 2.510 520 2.510 515 /+

    Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e

  • Atypical antipsychotic overdose: signs and symptoms

    Alpha-1:

    Dizziness, orthostatic hypotension, reflex tachycardia, miosis, nasal congestion

    Histamine-1:

    CNS depression, appetite stimulation, hypotension

    Muscarinic-1:

    Central agitation, hallucinations, memory dysfunction, dry skin and mucous membranes, hypertension, constipation, mydriasis, blurry vision, tachycardia, urinary retention

    20

  • Risk factors for type II diabetes

    Age 40 years

    First-degree relative with type 2 diabetes

    Member of high-risk population (e.g. people of Aboriginal, Hispanic, South Asian, Asian or African descent)

    History of IGT or IFG*

    Presence of complications associated with diabetes

    Vascular disease (coronary, cerebrovascular or peripheral)*

    History of gestational diabetes mellitus

    History of delivery of a macrosomic infant

    Hypertension*

    Dyslipidemia*

    Overweight*

    Abdominal obesity*

    Polycystic ovary syndrome*

    Acanthosis nigricans*

    Schizophrenia (The incidence of type 2 diabetes is at least 3 times higher in people with schizophrenia than in the general population)

    Other22 Canadian Diabetes Association

  • Cause of overweight or obese in patients with psychotic disorders

    Non-medical

    excessive food intake

    poor diet composition

    low physical activity

    Medical

    SGAs

    23

  • 24

  • 25

    ACUTE PSYCHOSIS MAINTENANCE METABOLIC SIDE EFFECTS

    Dosage Forms 1ST Episode Chronic 1ST Episode Chronic Weight Gain Lipids Glucose

    Atypical Antipsychotic Agents

    AripiprazoleO, S, ODT, IM

    1020 1530 1020 1530 /+

    AsenapineODT

    10 1020 10 1020 /+

    ClozapineO, ODT

    200600 400900 200600 300900 ++++ +++ +++

    IloperidoneO

    1224b 816 + /+ /+

    OlanzapineO, ODT, IM

    7.520 1030 7.515 1530 ++++ +++ +++

    PaliperidoneO

    69 612 39 615 + /+ /+

    Paliperidonepalmitate Depot IM

    See notec on dosing + /+ /+

    QuetiapineXR O

    200600 400900 200600 300900 + + /+

    RisperidoneO, S, ODT

    24 36 26 38 + /+ /+

    SertindoleO

    416 1220 1220 1232 /+

    ZiprasidoneO, IM

    120160 120200 80160 120200 /+

    Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e

  • 26

    NCEP:ATPIII 2001 IDF Criteria for Central AdiposityThree or more of the following: Waist circumference

    Central obesity: Waist circumference >102 cm

    (M), >88 cm (F)

    Men Women Ethnicity

    Hypertriglyceridemia: Triglycerides 150 mg/dL or

    specific medication

    94 cm 80 cm Europid, Sub-Saharan African, Eastern and Middle Eastern

    Low HDL cholesterol:

  • Copyright American Psychiatric Association. All rights reserved.

    From: Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis

    American Journal of Psychiatry 1999; 156:1686-1696

    95% Confidence IntervaIs for Weight Change After 10 Weeks on Standard Drug Doses, Estimated From a Random -Effects Model

    Figure Legend:

  • Side effects

    28

    Weight gain/ sedation

    Inactivity/obesity

  • 29

  • 30Clinical pharmacology & Therapeutics | VOLUME 90 NUMBER 1 | July 2011

  • 31Prim Care Companion J Clin Psychiatry 2004;6[suppl 2]:813

  • 32

  • 33

  • 34

  • 35

  • 36

  • 37

  • Monitoring protocol for patients on SGAs*

    38

    DIABETES CARE, VOLUME 27, NUMBER 2, FEBRUARY 2004

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